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Madelung's disease is a rare clinical disease with a low incidence. The main feature of the disease is lipodystrophy, which is more common in men between the ages of 30 and 60. At present, there is no standard and effective treatment for this disease in the world. Here, we reported a case of Madelung's disease with surgical treatment of the neck and reviewed relevant literature to improve the understanding of this disease. [ABSTRACT FROM AUTHOR]

The purpose of this paper was to explore the therapeutic effect and underlying mechanism of Tremella fuciformis polysaccharides (TFP) on ulcerative colitis (UC) based on dextran sodium sulfate (DSS)-induced mice UC model and lipopolysaccharide (LPS)-stimulated Caco-2 cells model. The results firstly indicated that TFP can significantly alleviate the symptoms and signs of the DSS-induced mice UC model, which manifests as improvement of body weight loss, increase of colon length, decrease of colon thickness and reduction of intestinal permeability. Then, results from histopathological and electron microscope analysis further implied that TFP could dramatically reduce inflammatory cells infiltration and restore intestinal epithelial barrier integrity. In addition, the experiments of LPS-stimulated Caco-2 cells model in vitro also further confirmed that TFP could markedly inhibit the expressions of pro-inflammatory cytokines and increase related genes or proteins expressions of intestinal barrier and mucus barrier. Taken together, these data suggested that TFP has a significant therapeutic effect on DSS-induced UC model, and its mechanisms are closely linked to the inhibition of inflammation and the restoration of intestinal barrier and mucus barrier function. These beneficial effects may make TFP a promising drug to be used in alleviating UC. • Polysaccharides from Tremella fuciformis (TFP) can attenuate ulcerative colitis (UC). • Mechanism of TFP on protecting against UC involved the inhibition of inflammation. • Mechanism of TFP on anti-UC was related to the restoration of intestinal barrier. • Mechanism of TFP on anti-UC was associated with increased mucus barrier function. [ABSTRACT FROM AUTHOR]

Glia modulate neuronal excitability and seizure sensitivity by maintaining potassium and water homeostasis. A salt inducible kinase 3 (SIK3)-regulated gene expression program controls the glial capacity to buffer K+ and water in Drosophila, however upstream regulatory mechanisms are unknown. Here, we identify an octopaminergic circuit linking neuronal activity to glial ion and water buffering. Under basal conditions, octopamine functions through the inhibitory octopaminergic G-protein-coupled receptor (GPCR) OctbR to upregulate glial buffering capacity, while under pathological K+ stress, octopamine signals through the stimulatory octopaminergic GPCR OAMB1 to downregulate the glial buffering program. Failure to downregulate this program leads to intracellular glia swelling and stress signaling, suggesting that turning down this pathway is glioprotective. In the eag shaker Drosophila seizure model, the SIK3-mediated buffering pathway is inactivated. Reactivation of the glial buffering program dramatically suppresses neuronal hyperactivity, seizures, and shortened life span in this mutant. These findings highlight the therapeutic potential of a glial-centric therapeutic strategy for diseases of hyperexcitability. [ABSTRACT FROM AUTHOR]

Background: Based on the consumers' attention issues of sea cucumbers, we aimed to complete comprehensive information of commercial Canadian sea cucumbers (CCSC), which sprang up extensively in Chinese food market. Results: CCSC were identified as Cucumaria frondosa and characterized based on the characteristics, nutritional compositions, and heavy metals. The abdomen and five internal tendons of Cucumaria frondosa were special orange. The average of soaking degree and water content, which consumers paid great attention to, was 2.8 ± 0.3 and 0.46 ± 0.09%, respectively. Proteins (56.4 ± 9.1%) and polysaccharides (12.2 ± 14.7%) were the principal nutrient component. In addition, there was a variety of free amino acids, in which arginine (70.1 ± 50.0 mg/100 g), glutamate (42.6 ± 23.9 mg/100 g), and alanine (32.2 ± 21.0 mg/100 g) were the main components. Phosphorus (P, 0.26 ± 0.05%), magnesium (Mg, 0.19 ± 0.07%), and kalium (K, 0.17 ± 0.08%) were the major mineral elements. Amount of heavy metal was within the safety limitation (5.5 ± 1.4 mg/kg). Furthermore, the active ingredients were positively correlated with size. Conclusion: The overall findings enriched the information of Cucumaria frondosa for consumers and suggested that the quality of Cucumaria frondosa was varied following commercial classification and size. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the stable effect and mechanism of sulfated polysaccharide from Undaria pinnatifida (SPUP) on atherosclerotic plaque. The results showed that atherosclerotic plaques in the ApoE−/− mice of high-fat diet model group increased significantly without drug intervention. The content of vulnerable components (lipid, inflammatory macrophage) increased significantly, and the content of stability components (smooth muscle cell, collagen) reduced significantly. However, it could find that atherosclerotic plaque areas were decreased in a dose-dependent manner after SPUP intervention. SPUP could enhance the dominance of the stability components in plaque, and reduce the content of vulnerable component. Furthermore, SPUP could significantly reduce the matrix metalloprotein-9 content in atherosclerotic plaque. These results suggested that SPUP could stabilize atherosclerotic plaque by enhancing the dominance of the stability components content, reducing the vulnerability components content, and lowering the vulnerability index value. • Sulfated polysaccharide from Undaria pinnatifida (SPUP) could stabilize atherosclerotic plaque. • SPUP could enhance the dominance of the stability components content (smooth muscle cell, collagen). • SPUP could decrease content of vulnerable components (lipid, inflammatory macrophage). • SPUP could significantly reduce the matrix metalloprotein-9 content in AS plaque. [ABSTRACT FROM AUTHOR]

Highlights • Polysaccharide (PPUS) from Polyporus umbellatus sclerotia had renoprotective effect. • PPUS had a noticeable protective effects on renal interstitial fibrosis. • The mechanism of PPUS treat renal fibrosis might be inhibit inflammation. • Mechanism of PPUS treat renal fibrosis was inhibit epithelial-mesenchymal transition. • Mechanism of PPUS treat renal fibrosis was rebalance of fibrotic/antifibrotic factor. Abstract As a fungal polysaccharide, polysaccharide (PPUS) from Polyporus umbellatus sclerotia have showed remarkable anti-inflammatory activities. In view of the closely relationship between inflammation and renal fibrosis, and considering the significant role of other fungal polysaccharides on treatment of renal fibrosis, we speculated that PPUS may have therapeutic effects on renal fibrosis. However, there was not any reports about PPUS treatment this disease. The purpose of this paper is to investigate renoprotective effect and mechanism of PPUS on renal fibrosis. The results indicated that PPUS can improve renal function and ameliorate the degree of renal collagen deposition and further fibrosis. Its mechanism was found to be related with decreased inflammation, suppressive epithelial-mesenchymal transition, reconstructed the balance of matrix metalloproteinases and tissue inhibitor of metalloproteinases, and pro-fibrotic and anti-fibrotic factors. The data implied that PPUS can serve as a clinical candidate on treatment of renal interstitial fibrosis. [ABSTRACT FROM AUTHOR]

Abstract Sulfated polysaccharide from Undaria pinnatifida (SPUP) has significant anti-breast cancer activity. However, its anticarcinogenic mechanism still remains unclear. The aim of this article is to observe the effect of SPUP on proliferation, migration and apoptosis of human breast cancer cell line MCF7. Firstly, the effect of SPUP on proliferation was evaluated through MTT assay, plate clonality assay and immunofluorescence test of PCNA. The results showed that SPUP could significantly reduce MCF7 cells proliferation in a time- and dose-dependent manner. Based on transwell and scratch wound healing assays, then, inhibitory action of SPUP for MCF7 cells migration was observed. Finally, apoptosis and cycle arrest of SPUP for MCF7 cells also were found by the results from both flow cytometry analysis and Hoechst 33342 staining of apoptotic cells. Overall, these results showed anti-breast cancer mechanism of SPUP could be possibly related to inhibit migration, proliferation and induce apoptosis of cancer cells. Highlights • Polysaccharide from Undaria pinnatifida (SPUP) could reduce MCF7 cells proliferation. • SPUP could significantly inhibit MCF7 cells migration. • SPUP could significantly promote MCF7 cells apoptosis. [ABSTRACT FROM AUTHOR]

Drug delivery systems have emerged as a prominent research focus in the field of drug development, offering enhanced stability and improved bioavailability. Among them, protein (silk, gelatin and whey) or polysaccharide (alginate, chitosan, cellulose, starch, pectin and carrageenan) aerogels derived from natural sources have gained increasing popularity due to their unique advantages, such as cost-effectiveness, flexible preparation, bioactivity, biocompatibility, and biodegradability. However, despite their growing significance, there remains a lack of comprehensive information and ongoing confusion regarding the application of protein/polysaccharide aerogels in drug delivery system. Hence, the objective of this review was to provide a comprehensive review of the research progress in protein/polysaccharide aerogels for drug delivery systems from the perspective of aerogels category, synthesis strategy, drug-loading method, performance characteristic and release mechanism. Furthermore, by consolidating the existing information, we aimed to present our own perspectives and insights on the future development of protein/polysaccharide aerogels in drug delivery system. In conclusion, this comprehensive review served as a valuable resource for researchers and scholars, addressing the current gaps in knowledge and clarifying the complex landscape of protein/polysaccharide aerogels in drug delivery system. [Display omitted] • Protein/polysaccharide aerogels are promising drug delivery carriers. • Protein/polysaccharide aerogels have advantages of wide source and bioactivities. • The research of protein/polysaccharide aerogels as drug carrier was reviewed. [ABSTRACT FROM AUTHOR]

Alkaloids are the most medicinally valuable ingredients in plant crop Coptis chinensis (C. chinensis). However, the separation of these small-molecule compounds is challenging because C. chinensis also contains a lot of impurities such as proteins and saccharides. Adsorption separation stands out in the field of biological separation by virtue of its efficiency and greenness. Here, this paper aimed to selectively separate the total alkaloids during extraction of C. chinensis by resorcinol-formaldehyde (RF) aerogel based on electrostatic interaction and size-sieving effect. First, RF aerogels with different surface area (40.6–674.9 m2/g) and pore size (2–25 nm approximately) were synthesized by adjusting the ratio of catalyst (C). The results of static adsorption showed that the optimum alkaloids selective separation was achieved at R/C of 10/1: alkaloids adsorption capacity (Q e), protein retention ratio (Pr), saccharides retention ratio (Sr) and the coefficient of selectivity were 487.93 mg/g, 87.40 %, 95.90 % and 2.23, respectively. Methanol containing 1 % hydrochloric acid was considered as the most suitable eluent with the desorption efficiency of 95.88 %. In addition, the adsorption process conformed to pseudo-second-order kinetics, intra-particle diffusion and Langmuir isotherm models, and was a spontaneous endothermic process. It was found from the dynamic adsorption experiment that the dynamic adsorption capacity was 497.81 mg/g, and the purity of total alkaloids increased from 39.19 % to 90.22 %. Compared with resin adsorption and salt precipitation method, RF aerogel separation could more efficiently separate the alkaloids from C. chinensis (the total alkaloids yield of 57.40 mg/g C. chinensis). In addition, the alkaloids separated by RF aerogel had better antioxidant and antibacterial activities than that separated by salt precipitation method. In summary, RF aerogel separation was potential as an efficient and green method for the separation of total alkaloids from C. chinensis. [Display omitted] • Resorcinol-formaldehyde (RF) aerogels with controlled pore size were synthesized. • RF aerogel was used to efficiently, greenly separate total alkaloids in C. chinensis. • The adsorption capacity and purity of total alkaloids reached 487.93 mg/g and 90.22 %. • Alkaloids adsorption on RF aerogel was result of electrostatic and size sieve effect. [ABSTRACT FROM AUTHOR]

Background: In an ECOG-ACRIN Cancer Research Group study (E1496), maintenance rituximab (MR) was reported to prolong progression-free survival (PFS) in comparison with observation (OBS) alone in patients with indolent lymphoma after induction chemotherapy. Here the long-term follow-up of the same patient cohort is presented.Methods: Patients with indolent lymphoma received induction chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP). Patients with stable disease or a better response were then randomized to weekly rituximab (375 mg/m(2) × 4 doses) every 6 months for 2 years (MR) or to OBS. The primary endpoint was PFS; the secondary endpoints were overall survival (OS), response rate, and toxicities.Results: Of the 387 patients who initially received CVP induction, 158 were randomized to MR, and 153 were randomized to OBS. After a median follow-up of 11.5 years, patients on MR had longer median PFS (4.8 years) than patients on OBS (1.3 years; hazard ratio [HR], 0.49; P < .0001). However, there was no difference in OS between MR and OBS (10-year OS, 67% vs 59%; median OS, 13.5 years vs not reached; HR, 0.91; P = .69). Other than MR, only minimal residual disease after induction therapy was significantly associated with PFS on multivariate analysis (HR, 0.71; P = .02). A low initial tumor burden, minimal residual disease, follicular histology, a low Follicular Lymphoma International Prognostic Index score, and female sex were associated with longer OS. There was no increase in the rate of second primary malignancies with MR vs OBS.Conclusions: With long-term follow-up, MR did not influence OS. The PFS benefit was maintained. MR should be considered optional for patients with indolent B-cell lymphoma. Cancer 2016;122:2996-3004. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

The International Prognostic Score ( IPS-7) is the most commonly used risk stratification tool for advanced Hodgkin lymphoma ( HL), however recent studies suggest the IPS-7 is less discriminating due to improved outcomes with contemporary therapy. We evaluated the seven variables for IPS-7 recorded at study entry for 854 patients enrolled on Eastern Cooperative Oncology Group 2496 trial. Univariate and multivariate Cox models were used to assess their prognostic ability for freedom from progression ( FFP) and overall survival ( OS). The IPS-7 remained prognostic however its prognostic range has narrowed. On multivariate analysis, two factors (age, stage) remained significant for FFP and three factors (age, stage, haemoglobin level) for OS. An alternative prognostic index, the IPS-3, was constructed using age, stage and haemoglobin level, which provided four distinct risk groups [ FFP ( P = 0·0001) and OS ( P < 0·0001)]. IPS-3 outperformed the IPS-7 on risk prediction for both FFP and OS by model fit and discrimination criteria. Using reclassification calibration, 18% of IPS-7 low risk patients were re-classified as intermediate risk and 13% of IPS-7 intermediate risk patients as low risk. For patients with advanced HL, the IPS-3 may provide a simpler and more accurate framework for risk assessment in the modern era. Validation of these findings in other large data sets is planned. [ABSTRACT FROM AUTHOR]

A persistently positive positron emission tomography ( PET) scan during therapy for diffuse large B-cell lymphoma ( DLBCL) is predictive of treatment failure. A response-adapted strategy consisting of an early treatment change to four cycles of R- ICE (rituximab, ifosfamide, carboplatin, etoposide) was studied in the Eastern Cooperative Oncology Group E3404 trial. Previously untreated patients with DLBCL stage III, IV, or bulky II, were eligible. PET scan was performed after three cycles of R- CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and scored as positive or negative by central review during the fourth cycle. PET-positive patients received four cycles of R- ICE, PET-negative patients received two more cycles of R- CHOP. A ≥45% 2-year progression-free survival ( PFS) for mid-treatment PET-positive patients was viewed as promising. Of 74 patients, 16% were PET positive, 79% negative. The PET positivity rate was much lower than the 33% expected. Two-year PFS was 70%; 42% [90% confidence interval (CI), 19-63%] for PET-positives and 76% (90% CI 65-84%) for PET-negatives. Three-year overall survival ( OS) was 69% (90% CI 43-85%) and 93% (90% CI 86-97%) for PET-positive and -negative cases, respectively. The 2-year PFS for mid-treatment PET-positive patients intensified to R- ICE was 42%, with a wide confidence interval due to the low proportion of positive mid-treatment PET scans. Treatment modification based on early PET scanning should remain confined to clinical trials. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the activity of topotecan given by 21-day continuous infusion in patients previously treated with one prior therapy for a diffuse large-cell lymphoma or immunoblastic lymphoma. Patients with appropriate histology and measurable disease who had been treated with one prior chemotherapy regimen were eligible for study. Slides of tumor biopsies were submitted for central review of pathology. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 and adequate bone marrow function. Patients were treated with continuous infusion topotecan, 0.4 mg/m2/day × 21 days. Therapy could be escalated to 0.5 and then 0.6 mg/m2/day in subsequent cycles if there was no dose-limiting toxicity at the initial dose level. Patients were treated with two cycles after achieving a complete response or until disease progression or unacceptable toxicity occurred. Thirty-seven patients were enrolled. However, only 26 cases were eligible due to a performance status of > 2 ( n = 2), more than one prior chemotherapy ( n = 1) and wrong histology on review ( n = 8). Due to the unexpectedly high ineligibility rate, two sets of analysis were done for all 37 patients enrolled and for the 26 eligible patients, respectively. Of the 37 patients (15 males and 22 females), the International Prognostic Index included 11% low risk, 30% low intermediate risk, 46% high intermediate risk and 8% high risk. The median follow-up was 77 months. A total of 136 cycles of therapy were given with a median of 3 cycles per patient. Grade 4 toxicities included: 14% grade 4 thrombocytopenia; 14% grade 4 granulocytopenia, 8% leukopenia, 3% each anemia, hemorrhage, infection, vomiting, thrombosis, liver toxicity and neuromotor toxicity. The response analysis including all 37 patients showed five complete responses (CRs) and four partial responses (PRs) for a total response rate of 24% (90% two-stage confidence interval 13-39%). Median progression-free survival (PFS) was 3.7 months, with 1- and 2-year PFS of 21% and 6%, respectively (90% confidence interval 11-34% and 2-15%). Median overall survival (OS) was 10.5 months, with 1- and 2-year OS of 41% and 27%, respectively (90% confidence interval 27-53% and 16-39%). Analysis including only eligible patients showed similar response rates and survival outcomes. Single agent topotecan has moderate activity for previously treated high-grade lymphoma equivalent to that of several newer agents, and should be considered for incorporation into multi-drug salvage chemotherapy programs. [ABSTRACT FROM AUTHOR]

The article presents a study which determines the activity as well as the toxicity of sorafenib in a multi-institutional setting in patients who were given the treatment with one prior chemotherapy regimen. Study shows no therapy-related deaths nor was an effective second-line systemic chemotherapy for patients. It is concluded that investigation of tyrosine kinase inhibitors is warranted through the use of different trial designs.

The rapid emergence of Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) variants, coupled with severe immune evasion and imprinting, has jeopardized the vaccine efficacy, necessitating urgent development of broad protective vaccines. Here, we propose a strategy employing recombinant rabies viruses (RABV) to create a universal SARS-CoV-2 vaccine expressing heterologous tandem receptor-binding domain (RBD) trimer from the SARS-CoV-2 Prototype, Delta, and Omicron strains (SRV-PDO). The results of mouse immunization indicated that SRV-PDO effectively induced cellular and humoral immune responses, and demonstrated higher immunogenicity and broader SARS-CoV-2 neutralization compared to the recombinant RABVs that only expressed RBD monomers. Moreover, SRV-PDO exhibited full protection against SARS-CoV-2 in the challenge assay. This study demonstrates that recombinant RABV expressing tandem RBD-heterotrimer as a multivalent immunogen could elicit a broad-spectrum immune response and potent protection against SARS-CoV-2, making it a promising candidate for future human or veterinary vaccines and offering a novel perspective in other vaccine design. • A recombinant RABV vaccine expressing the SARS-CoV-2 RBD-heterotrimer was developed. • The recombined RABV induced broad-spectrum neutralizing antibodies and showed full protection in SARS-CoV-2 challenge. • Tandem RBD not only enhances its immunogenicity, but also contains more epitopes associated with immune escape. [ABSTRACT FROM AUTHOR]

• An effective method of anthocyanins from blueberry (Vaccinium spp.) was developed. • Anthocyanins was extracted by freeze-ultrasound thawing extraction (FUTE). • Anthocyanins from blueberry (Vaccinium spp.) by FUTE had higher extraction rate. • Anthocyanins from blueberry (Vaccinium spp.) by FUTE had stronger antioxidation. The aim of this study was to develop an effective method for extracting anthocyanins from blueberry Vaccinium spp. (ABVS) using freeze-ultrasonic thawing technology (FUTE). Various parameters including freezing time, ultrasonic time, ultrasonic temperature and liquid–solid ratio were optimized by a single-factor design and multiple response surface methodology. The amounts of extracted anthocyanin and cyanidin-3-O-glucoside were measured by UV and HPLC respectively. The maximum yield of anthocyanins was achieved by freezing the samples for 5.43 min in liquid nitrogen at the liquid–solid ratio of 24.07:1 mL/g, followed by ultrasonic thawing at 41.64 °C for 23.56 min. The yield and antioxidant effects of ABVS extracted using FUTE, ultrasound-assisted extraction (UAE) and freeze-thawing extraction (FTE) were compared in order to determine the overall efficacy of FUTE. In addition to the higher content, FUTE extracted ABVS showed greater ability to scavenge DPPH·, ABTS+ and superoxide anions, and inhibit lipid peroxidation compared to the ABVS extracted by UAE or FTE. The reducing power of the FUTE-derived ABVS was intermediate between that of the UAE and FTE samples. Taken together, FUTE can rapidly and effectively extract ABVS and retain its antioxidant capacity. [ABSTRACT FROM AUTHOR]

Polysaccharides (PMM) from Meretrix meretrix Linnaeus exhibit a variety of biological activities; however, conventional purification methods are costly, time consuming and introducing toxic agents. This paper aimed to develop a green and efficient method for the deproteinization of PMM by copper ion chelating aerogel (CCA) adsorption. First, CCA was successfully prepared by copper ion chelating composite aerogel (CA). Then, CCA adsorption was applied to remove protein mixed in PMM. The optimal parameter conditions of this deproteinization method were screened, using the deproteinization rate (D r %), polysaccharide recovery rate (R r %) and selectivity coefficient (K c) as evaluation indicators, by single factor experiment. The optimal conditions were obtained as follows: CCA dose of 1.4%, pH value of 5.0 and adsorption temperature of 30 °C. Under these conditions, equivalent D r % (93.31 ± 1.33%), higher R r % (93.34 ± 1.08%) and K c (14.01 ± 0.46) were achieved compared with the latest reported deproteinization report. Finally, the effect of deproteinization between CCA adsorption and Sevag method, which is the most classical deproteinization method, were compared to verify the practicability of CCA adsorption. As a result, CCA adsorption not only showed much higher R r % as well as K c , but also would not cause any reagent contamination and environment pressure. In conclusion, CCA adsorption would be a green and highly efficient method with great potential in large-scale environmentally sustainable deproteinization of polysaccharides in the future. Image 1 • Copper ion chelating aerogel (CCA) was successfully prepared. • CCA was a green deproteinization way for crude polysaccharide (PMM). • CCA was also an efficient deproteinization method for PMM. [ABSTRACT FROM AUTHOR]

Intact epithelial barrier and mucosal immune system are crucial for maintaining intestinal homeostasis. Previous study indicated that Dendrobium officinale polysaccharides (DOPS) can regulate immune responses and inflammation to alleviate experimental colitis. However, it remains largely unknown whether DOPS can suppress AOM/DSS-induced colorectal cancer (CRC) model through its direct impact on intestinal barrier function and intestinal mucosal immunity. Here, we demonstrated the therapeutic action of DOPS for CRC model and further illustrated its underlying mechanisms. Treatment with 5-aminosalicylic acid (5-ASA) and DOPS significantly improved the clinical signs and symptoms of chronic colitis, relieve colon damage, suppress the formation and growth of colon tumor in CRC mice. Moreover, administration of DOPS effectively preserved the intestinal barrier function via reducing the loss of zonula occludens-1 (ZO-1) and occludin in adjacent tissues and carcinomatous tissues. Further studies demonstrated that DOPS improved the metabolic ability of tumor infiltrated CD8+ cytotoxic T lymphocytes (CTLs) and reduced the expression of PD-1 on CTLs to enhance the anti-tumor immune response in the tumor microenvironments (TME). Together, the conclusions indicated that DOPS restore intestinal barrier function and enhance intestinal anti-tumor immune response to suppress CRC, which may be a novel strategy for the prevention and treatment of CRC. [ABSTRACT FROM AUTHOR]

Purpose: Inborn errors of IFN-γ immunity underlie Mendelian susceptibility to mycobacterial disease (MSMD). Twenty-two genes with products involved in the production of, or response to, IFN-γ and variants of which underlie MSMD have been identified. However, pathogenic variants of IFNG encoding a defective IFN-γ have been described in only two siblings, who both underwent hematopoietic stem cell transplantation (HCST). Methods: We characterized a new patient with MSMD by genetic, immunological, and clinical means. Therapeutic decisions were taken on the basis of these findings. Results: The patient was born to consanguineous Turkish parents and developed bacillus Calmette-Guérin (BCG) disease following vaccination at birth. Whole-exome sequencing revealed a homozygous private IFNG variant (c.224 T > C, p.F75S). Upon overexpression in recipient cells or constitutive expression in the patient's cells, the mutant IFN-γ was produced within the cells but was not correctly folded or secreted. The patient was treated for 6 months with two or three antimycobacterial drugs only and then for 30 months with subcutaneous recombinant IFN-γ1b plus two antimycobacterial drugs. Treatment with IFN-γ1b finally normalized all biological parameters. The patient presented no recurrence of mycobacterial disease or other related infectious diseases. The treatment was well tolerated, without the production of detectable autoantibodies against IFN-γ. Conclusion: We describe a patient with a new form of autosomal recessive IFN-γ deficiency, with intracellular, but not extracellular IFN-γ. IFN-γ1b treatment appears to have been beneficial in this patient, with no recurrence of mycobacterial infection over a period of more than 30 months. This targeted treatment provides an alternative to HCST in patients with complete IFN-γ deficiency or at least an option to better control mycobacterial infection prior to HCST. [ABSTRACT FROM AUTHOR]

Background/Aims: Rhabdomyolysis (RM) is a potentially life-threatening condition that results from the breakdown of muscle and consequent release of toxic compounds into circulation. The most common and severe complication of RM is acute kidney injury (AKI). This study aimed to evaluate the efficacy and mechanisms of action of curcumin-loaded nanoparticles (Cur-NP) for treatment of RM-induced AKI. Methods: Curcumin-NP was synthesized using the nanocarrier distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) to achieve a prolonged and constant drug release profile compared with the curcumin-free group. The anti-AKI effects of Curcumin-NP were examined both in vitro (myoglobin-treated renal tubular epithelial HK-2 cells) and in vivo (glycerol-induced AKI model). Results: Our results indicated that Curcumin-NP reversed oxidative stress, growth inhibition and cell apoptosis accompanied with down-regulation of apoptotic markers Caspase-3 and GRP-78 in vitro. In vivo studies revealed enhanced AKI treatment efficacy with Curcumin-NP as characterized by reduced serum creatine phosphokinase (CPK), creatinine (Cr) and urea and less severe histological damage in renal tubules. In addition, kidney tissues from Curcumin-NP-treated AKI rats exhibited reduced oxidative stress, apoptosis, and cleaved Capase-3 and GRP-78 expression. Conclusion: Our results suggest that nanoparticle-loaded curcumin enhances treatment efficacy for RM-induced AKI both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Background: Rabies, caused by the rabies virus (RABV), is an ancient and neglected zoonotic disease posing a large public health threat to humans and animals in developing countries. Immunization of animals with a rabies vaccine is the most effective way to control the epidemic and the occurrence of the disease in humans. Therefore, the development of cost-effective and efficient rabies vaccines is urgently needed. The activation of dendritic cells (DCs) is known to play an important role in improving the host immune response induced by rabies vaccines. Methodology/Principal findings: In this study, we constructed a recombinant virus, rCVS11-MAB2560, based on the reverse genetic system of the RABV CVS11 strain. The MAB2560 protein (a DC-targeting molecular) was chimeric expressed on the surface of the viral particles to help target and activate the DCs when this virus was used as inactivated vaccine. Our results demonstrated that inactivated rCVS11-MAB2560 was able to promote the recruitment and/or proliferation of DC cells, T cells and B cells in mice, and induce good immune memory after two immunizations. Moreover, the inactivated recombinant virus rCVS11-MAB2560 could produce higher levels of virus-neutralizing antibodies (VNAs) in both mice and dogs more quickly than rCVS11 post immunization. Conclusions/Significance: In summary, the recombinant virus rCVS11-MAB2560 chimeric-expressing the molecular adjuvant MAB2560 can stimulate high levels of humoral and cellular immune responses in vivo and can be used as an effective inactivated rabies vaccine candidate. Author summary: Due to the lack of effective treatments and drugs, rabies is still an important zoonotic disease, posing a great risk to animals and human public health in developing countries. Vaccines, especially inactivated vaccines, are currently the most effective way to prevent and control the rabies epidemic. Here, we constructed a recombinant virus rCVS11-MAB2560 chimeric-expressed MAB2560 protein (a DC-targeting molecular) on the surface of the RABV particles to promote its immunogenicity in vivo by activating the dendritic cells (DCs) and enhancing antigen uptake. Our results showed that inactivated rCVS11-MAB2560 was able to promote the recruitment and/or proliferation of DC cells, T cells and B cells in mice, and induce good immune memory after two immunizations. Moreover, compared with rCVS11, the inactivated recombinant virus rCVS11-MAB2560 could induce higher level of virus-neutralizing antibodies (VNAs) in mice and dogs more quickly post immunization. rCVS11-MAB2560 thus has potential to be used as a promising candidate for an effective inactivated rabies vaccine. [ABSTRACT FROM AUTHOR]

Renal fibrosis (RF) is the common pathway for a variety of chronic kidney diseases that progress to end-stage renal disease. Chitosan oligosaccharide (COS) has been identified as possessing many health functions. However, it is not clear whether COS can prevent RF. The purpose of this paper was to explore the action and mechanism of COS in alleviating RF. First, an acute unilateral ureteral obstruction operation (UUO) in male BALB/c mice was performed to induce RF, and COS or fosinopril (positive control drug) were administered for 7 consecutive days. Data from our experiments indicated that COS treatment can significantly alleviate kidney injury and decrease the levels of blood urea nitrogen (BUN) and serum creatinine (SCr) in the UUO mouse model. More importantly, our results show that COS can reduce collagen deposition and decrease the expression of fibrosis proteins, such as collagen IV, fibronectin, collagen I, α-smooth muscle actin (α-SMA) and E-cadherin, ameliorating experimental renal fibrosis in vivo. In addition, we also found that COS suppressed oxidative stress and inflammation in RF model mice. Further studies indicated that the mechanism by which COS alleviates renal fibrosis is closely related to the regulation of the TGF-β1/Smad pathway. COS has a therapeutic effect on ameliorating renal fibrosis similar to that of the positive control drug fosinopril. Taken together, COS can alleviate renal fibrosis induced by UUO by reducing oxidative stress damage and regulating the TGF-β1/Smad pathway. [ABSTRACT FROM AUTHOR]

In this study, different extraction methods of polysaccharides from Crataegus pinnatifida Bunge (CPP) were compared by studying the extraction yield, structural characteristics and antioxidant activities. Firstly, polysaccharides were obtained using hot water extraction (CPPh), ultrasound assisted extraction (CPPu), enzyme assisted extraction (CPPe) and enzyme-ultrasound assisted extraction (CPPc), respectively. Meanwhile, the optimum extraction conditions of enzyme-ultrasonic assisted extraction were determined by response surface method (RSM). The extraction yields, structural characteristics and antioxidant activities were investigated and compared by visual photos, gas chromatography, ultraviolet-visible and Fourier-transform infrared spectroscopy. The results clearly showed that enzyme-ultrasonic assisted extraction possessed the highest extraction yield (10.39 ± 0.04%). The molecular weight of CPPh was the highest while the other polysaccharides had no significant difference. Besides, the monosaccharide composition of CPPc, CPPh, CPPu and CPPe were similar but the molar percentages of monosaccharide were different. Finally, the results of antioxidant activities showed that CPPc exhibited the highest scavenging effect of superoxide radical and lipids inhibiting ability. In summary, enzyme-ultrasonic assisted extraction was a high-efficient and low-energy consumption method for CPP extraction. • Four methods were used to extract polysaccharides from C. pinnatifida (CPP). • Enzyme-ultrasound assisted extraction method was optimized and had higher yield. • The structure characterization of CPP from different extraction was analyzed. • The antioxidant activities of CPP from different extraction were compared. [ABSTRACT FROM AUTHOR]

The further development of fishery resources is a hotspot in the development of the fishery industry. However, how to develop aquatic animal resources deeply is a key point to be solved in the fishery industry. Over the past decades, numerous aquatic animals have gained great attention in the development and utilization of their bioactive molecules which are of therapeutic applications as nutraceuticals and pharmaceuticals. Recent research revealed that aquatic animals are composed of many vital moieties, such as polysaccharides and proteins, which provide health benefits beyond basic nutrition. In particular, aquatic animal polysaccharides are gaining worldwide popularity owing to their high content, ease of extraction, specific structure, few side effects, prominent therapeutic potential and incorporation in functional foods and dietary supplements. Thus, tremendous research on the isolation, identification and bioactivities of polysaccharides has been carried out. This review presents comprehensive viewpoints on extraction, separation, purification, structural characterization and bioactivity of various polysaccharides from aquatic animals, such as sea cucumber, abalone, oyster and mussels. In addition, this review profiled a brief knowledge on both current challenges and future scope in aquatic animal polysaccharides field. The review will be a direction of deep processing in fishery resources, which is a hotspot, but technical bottleneck. Furthermore, the review could be served as a useful reference material for further investigation, production and application of polysaccharides from aquatic animals in functional foods and therapeutic agents. [ABSTRACT FROM AUTHOR]

Dendrobium officinale polysaccharides (DOP) has been reported to possess remarkable effects on improving renal function, oxidative stress damage and fibrotic diseases. However, the role and mechanism of DOP in preventing and treating renal fibrosis remain unclear. The purpose of this paper was to explore the therapeutic effects and underlying mechanisms of DOP on renal fibrosis. Firstly, renal fibrosis model was induced by unilateral ureteral obstruction operation (UUO) in male BALB/c mice. Subsequently, the anti-renal fibrosis effect of DOP was evaluated. It turned out that DOP significantly attenuated UUO induced renal fibrosis. The beneficial effects of DOP on renal fibrosis were concretely manifested in the relief of clinical symptoms, improvement of renal function, reduction of extracellular matrix collagen aggregation, attenuation of structural damage and inflammation, and decrement of profibrotic factors secretion. Meanwhile, DOP could also alleviate oxidative stress injury and inhibit the AhR/NOX4 pathway proteins expression. Furthermore, multivariate statistical analysis, AhR interference and overexpression experiments showed that the effect of DOP on alleviating renal fibrosis was closely related to the improvement of oxidative stress injury mediated by the AhR/NOX4 pathway. Overall, the data in the present paper indicated that DOP could alleviate renal fibrosis through improving AhR/NOX4 mediated oxidative stress injury. [Display omitted] • The Dendrobium officinale polysaccharides (DOP) could improve renal fibrosis (RF). • DOP could relieve the state of oxidative stress injury induced by RF. • DOP could regulate AhR/NOX4 pathway abnormal activation induced by RF. • Anti-RF role of DOP was related to AhR/NOX4 pathway mediated oxidative stress injury. [ABSTRACT FROM AUTHOR]

Abstract The purpose of this paper was to investigate the effects and mechanism of polysaccharide (PAOF) from Alpiniae oxyphyllae fructus on urinary incontinence (UI) in old-age hydruric model rats (OHMR). Results suggested that PAOF can significantly reduce the urination volume, Na+, Cl− emission and increase K+ excretion of OHMR. In addition, PAOF can increase the content of aldosterone (ALD) and antidiuretic hormone (ADH) in blood of OHMR. The coefficients of spleen, thymus and adrenal of OHMR were improved by PAOF. Furthermore, PAOF can not only elevate significantly the expression of β3-adrenoceptor mRNA in bladder detrusor of OHMR, but also increase the content of adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in bladder detrusor of OHMR. Meanwhile, PAOF can elevate significantly the expression of PKA protein in bladder detrusor of rats with polyuria. The data implied that PAOF may offer therapeutic potential against UI. [ABSTRACT FROM AUTHOR]

Background Randomised trials of rituximab maintenance (MR) for patients with follicular lymphoma support improved progression-free survival (PFS), but the effect on overall survival has been inconclusive. To evaluate the effect of MR on overall survival according to patient and disease characteristics, and to explore certain adverse events, we performed an individual patient data (IPD) meta-analysis. Methods All investigators of randomised controlled trials that compared MR therapy with observation or treatment only at relapse (no MR) for patients with follicular lymphoma were invited to participate in an IPD meta-analysis. We obtained baseline patient and disease characteristics and time to progression and death for each patient. All analyses took into account the trial and original randomised treatment group. We analysed data in two ways: a two-stage analysis and a multivariate model including patient and disease characteristics. Findings Seven trials including 2315 patients were analysed. Overall survival of patients improved with MR compared with no MR (hazard ratio [HR] 0.79, 95% CI 0.66–0.96). We could not detect any patient or disease characteristics that were associated with a survival benefit with MR. In all of the models, MR had a beneficial effect on overall survival compared with observation for all types of patients, which was not shown in a particular subgroup in which the patient had already received rituximab in the induction phase and received first-line therapy. MR improved PFS compared with observation (HR 0.57, 95% CI 0.51–0.64). The risk of adverse events was higher with MR, specifically infection of any grade and grade 3–4 infections. Interpretation Based on IPD from randomised controlled trials, MR improves overall survival consistently in all patients, regardless of patient and disease characteristics when compared with observation, and should be prescribed after a successful induction with R-CVP or R-CHOP for patients with follicular lymphoma. It is still uncertain if that holds when the patient has already received rituximab in his/hers first induction. The effect of MR after bendamustine-rituximab induction compared with rituximab at progression should be further explored. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Dysphagia is a common side effect following chemoradiation therapy (CRT) in head and neck cancer (HNC) patients. Current dysphagia management includes swallowing therapy and dilation procedures, but these treatments have limitations. While acupuncture has been reported to positively impact swallowing function and quality of life (QOL) in patients with dysphagia, current evidence is inconclusive. Material and methods: In an ongoing trial, 42 squamous cell carcinoma HNC patients, who are receiving platinum-based CRT with curative intent, are being recruited from a comprehensive cancer center. They are randomized to 12 sessions of either active acupuncture or to sham acupuncture during and following CRT over a 24-week period. Blinded research staff assesses outcomes at baseline, 20weeks post-CRT (end of acupuncture), and 12months after baseline (6-month follow-up). The primary outcome is change in M.D. Anderson Dysphagia Inventory score from baseline to 12months. Secondary outcomes include QOL measures pertaining to HNC patients. In addition, a subset of study patients are tested for salivary flow rates and cytokines, including plasma transforming growth factor-β1 and interleukin 6 (n=10 per arm), to preliminarily explore the biological mechanisms of acupuncture for dysphagia. Discussion: This paper addresses unique challenges related to study design in nonpharmacological, sham-controlled acupuncture trials including development of evidence-based credible verum and sham treatment protocols, blinding, and assuring fidelity of treatment. Results of this study will inform the feasibility of conducting a large scale trial and will provide preliminary evidence regarding the value of acupuncture for dysphagia in HNC patients. [Copyright &y& Elsevier]

Background: There is no effective second-line systemic chemotherapy for patients with disease progression after cisplatin-based chemotherapy. A phase 2 trial of sorafenib was performed to determine the activity and toxicity of this agent in a multi-institutional setting in patients previously treated with 1 prior chemotherapy regimen.Methods: Twenty-seven patients with advanced urothelial carcinoma were treated with sorafenib 400 mg orally twice daily continuously until progression or unacceptable toxicity.Results: There were no objective responses observed. The 4-month progression-free survival (PFS) rate was 9.5%; median overall survival of the group was 6.8 months. There were no therapy-related deaths, and common grade 3 toxicities included fatigue and hand-foot syndrome.Conclusions: Although sorafenib as a single agent has minimal activity in patients with advanced urothelial cancer in the second-line setting, further investigation of tyrosine kinase inhibitors using different trial designs with PFS endpoints is warranted. [ABSTRACT FROM AUTHOR]

Background: There is a need to identify active new regimens in patients with advanced urothelial cancer. Pemetrexed and gemcitabine are active agents in advanced urothelial cancer. A phase 2 trial of the combination of these 2 agents was performed in patients with advanced urothelial cancer who were previously untreated for metastatic disease.Methods: Forty-six patients with advanced urothelial carcinoma received pemetrexed disodium 500 mg/m2 and gemcitabine 1000 mg/m2 intravenously on Day 1, with gemcitabine repeated on Day 8. Cycles were repeated every 3 weeks for a maximum of 6 cycles.Results: Two patients attained a complete response, and 12 patients attained a partial response for an overall response rate of 31.8% (90% confidence interval, 20.4%-45.2%). The median time to disease progression was 5.8 months, and the median overall survival was 13.4 months. Thirty-three patients (75%) experienced grade>or=3 neutropenia, and 5 patients (11%) had febrile neutropenia. There were 2 therapy-related deaths.Conclusions: The combination of pemetrexed and gemcitabine had moderate antitumor activity in previously untreated patients with advanced urothelial cancer at the expense of significant myelosuppression. [ABSTRACT FROM AUTHOR]

Tetracycline hydrochloride (TC) wastewater has complex components, high concentration of organic matter and certain biological toxicity. Photocatalytic degradation is of great application prospect due to its green, thorough and efficient removal of TC. In this study, heterojunction photocatalyst supported on Palygorskite (Pal) AgBr–TiO 2 -Pal with visible light response was successfully prepared via sol-gel and liquid deposition method successfully. Taking TC as the target pollutant, the photocatalytic performance of AgBr–TiO 2 -Pal photocatalys excited by visible light was studied. The spreading/grafting of AgBr–TiO 2 on the surface of Pal was improved by a series of structural characterization and composition analysis. The results also demonstrated that the specific surface area of AgBr–TiO 2 -Pal was about 48.06 m2⋅g−1 with uniform mesoporous slit. The AgBr–TiO 2 -Pal catalyst was very effective for the degradation of TC, and it still retained its high stability and reusability after five cycles. The results showed that under the best reaction conditions (initial concentration of tetracycline 10 mg⋅L−1, catalyst dosage 0.5 g⋅L−1, pH value 9), with the excitation of visible light, the maximum removal ratio of TC was 90%, and the mineralization ratio was 67%. The removal efficiency and degradation rate of TC by AgBr–TiO 2 -Pal catalyst were 2.17 and 4.75 times as much as those of TiO 2 respectively. The outstanding photocatalytic performance of heterogeneous AgBr–TiO 2 -Pal catalyst was obtained by fully participate in the reaction by photoinduced charge. This study could be expected to be used in photocatalytic degradation of antibiotic pollutants in wastewater treatment. • A novel AgBr–TiO 2 -Pal photocatalyst is prepared for tetracycline degradation. • The catalyst support, Palygorskite, has a porous structure and large surface area. • The AgBr–TiO 2 heterostructure has enhanced visible light photocatalytic activity. • The catalyst can be recycled more than five times by a simply filtered. [ABSTRACT FROM AUTHOR]

Background: In patients with diabetes mellitus, the urinary microalbumin-to-urine creatinine ratio (UACR) can not only predict the occurrence of diabetic nephropathy but also can be a risk factor for cardiovascular disease and renal function damage. Current studies on subclinical hypothyroidism (SCH) and UACR are mainly cross-sectional studies, and the results suggest that SCH is an independent risk factor for UACR. To further explore the longitudinal effect of SCH on UACR, we carried out this study. Methods: This was a retrospective cohort study including 46 patients with type 2 diabetes mellitus and SCH in the Department of Endocrinology, The Affiliated Huai'an Hospital of Xuzhou Medical University from January 2013 to April 2018. At the same time, 96 patients with type 2 diabetes mellitus and euthyroid were chosen according to 1:2 approximately matched with age, sex and duration of diabetes mellitus. Univariate analysis, stratified analysis, and multiple linear regression analysis were used to investigate the effect of SCH on ΔUACR(ΔUACR = UACR after 1 year - baseline UACR) in patients with type 2 diabetes mellitus. Results: There was no significant difference between the baseline UACR, (p > 0.05). However, the ΔUACR was significantly higher in SCH group than euthyroid group, as shown by univariate analysis, stratified analysis and multiple linear regression analysis (β:-1.071, 95% CI: − 1.713--0.428), and the difference was statistically significant (all p < 0.05). Conclusion: SCH is associated with an increased UACR in type 2 diabetes mellitus patients. It is necessary to screen for thyroid function in type 2 diabetes mellitus and increase the follow-up frequency of UACR in patients with SCH. [ABSTRACT FROM AUTHOR]